Sequential and reinforcement learning for demand side management by Margaux B...
BCG effectiveness in preventing TB
1. Efficacy of BCG Vaccine in
the Prevention of Tuberculosis
A Meta-analysis Review
Barbara Waldorf
Laura Hajar
Abby Link
Scott Shatzman
(Last names were taken from Gmail - if wrong, my apologies
and please fix)
2. Background and Public Health
Significance
• Highly contagious,
airborne disease
– High mortality and
morbidity
– Responsible for more
adult deaths than any
other pathogen
• Declared a global
emergency by WHO in
1993
3. • Predominantly in the developing world
– Areas of poverty
• Refugee camps, prisons, etc.
– Overcrowded living conditions
• 2 BILLION people worldwide are infected with TB
– 1/10 will go to develop the disease
– 9.4 million people developed active TB last year (WHO)
– Global incidence of TB reached its peak in 2004 (142/100,000)
4. BCG - Front Line of TB Control
• BCG
– Vaccine was created in 1908 and
first used in 1921
– Most widely used vaccine in the
world
• 3 billion doses given
– Only vaccine currently available for
TB
• Efficacy
– More effective against disseminated
and meningeal disease in youth
than pulmonary disease in adults
– Protective against leprosy,
meningtitis
• Controversy
– Question to overall efficacy
– Duration of protective immunity
– Impact of age of vaccination on
protection
– Efficacy of individual strains of BCG
5. • Dr. Graham A. Colditz
• Published in the Journal
of American Medicine
Association (JAMA)
– March 2nd
, 1994
• Objective was to
quantify the efficacy of
BCG vaccine against
TB
– Reviewed 1264 articles
from MEDLINE
– 70 articles reviewed in
depth
– Analyzed
• 14 prospective trials
• 12 case control studies
6. Summary
• BCG vaccination performance in prospective
trials has ranged from possibly detrimental to
an 80% protective benefit
• 10 case control studies showed efficacy in
preventing TB
– However, protection range was from 2%-90%!
• Confidence in BCG was rocked by the
Madras trial
– BCG vaccine failed to show any benefit against
pulmonary TB
– However, still the recommendation of WHO
7. Unanswered Questions
• Overall efficacy
• The duration of protective immunity
• How age at vaccination affects protection
• This study undertook a meta-analysis to test
the hypothesis that rates of TB are different in
BCG-vaccinated and BCG-non-vaccinated
control populations
– In addition, aimed to derive overall efficacy rates
for BCG vaccination
8. Methodology
• Identification of trials:
– computerized keyword search on MEDLINE using
terms BCG vaccine, tuberculosis, human
– contacted experts on BCG vaccination
• Inclusion Criteria:
– studies measuring efficacy of BCG vaccination in
preventing TB cases and/or death
– studies on prevalence, control, reviews were
searched for relevant references
– trials that randomly established concurrent
comparison groups receiving and not receiving
BCG vaccine
9. Data Extraction and Validity Scoring
• For Each Study
– year of publication - year vaccination began - study design
– age range of study population - sample size - location of study
– strain and dose of BCG used - route of administration
– follow-up time or time since immunization - outcomes measured
– efficacy of vaccine
• Studies represent a 60 year time span and reflect changes in
medical practice, reporting techniques, and design and conduct
of studies
– in trials, scoring system assessed:
• method of vaccine assignment to study population
• availability for follow-up
• equality of surveillance among both study arms
• criteria for diagnosis of TB
– preparation of BCG vaccine
• All scoring done a priori of analysis of results
10. Statistical Analysis
• random effect models used to obtain summary estimates of relative risk or odds
ratio from a group of studies, stratified subsets of trials and studies where the
outcome, age at vaccination, methods used for diagnosis, or study design
defined the stratification
• studies were further divided into three categories based on method of allocation
subject to groups: random, alternate, or systematic
• random effects regression model to look at sources of heterogeneity in efficacy
of BCG vaccine reported
• results from prospective trials presented as relative risk, odds ratio in case-
control
• investigators repeated meta-analysis computations of TB cases from the 13
prospective trials, adding 20 hypothetical trials each equal in size to the single
largest trial and each showing no benefit from BCG vaccine. The efficacy of
BCG remained statistically significant even with inclusion of these hypothetical
trials.
– their findings remained constant
12. Results
BCG PE of preventing TB was 51%. RR 0.49 (0.34-0.70) from 13 trials
(random, alternate and systematic allocation)
BCG PE against TB compared to no vaccination was 50% from 10 case-control
studies involving 1414 subjects. OR 0.5 (0.39-0.64)
Among 13 prospective trials, geographic latitude and study validity score
explained 66% of the between study variance in the trials. With efficacy of
BCG vaccination increasing with increased distance from the equator.
The data validity score was the only variable in a random-effects regression
model that explained a substantial amount (36%) of heterogeneity.
13. Analysis of Results
• The clinical trials were published from 1948-1980.
• Data outlier of 1.56, typical RR of cases of TB ranging from 0.20-1.01 in clinical
trials (can skew data)
• 8 out of 13 clinical trial studies had < 50 cases of TB with BCG and without BCG
• 9 out of 13 clinical trials had < 90 cases of TB for data analysis
• Data validity score- assesses for potential bias in study design and ascertainment of
diagnosis. Heterogeneity was found in biases
• Variance in study size for Clinical Trials: 262-17,6782 Case Control: 282-1,847
• Differences unclear between the case and control groups in Case-Control Studies
Notas do Editor
An objective of the study needs to be done before this summary
p. 669, 3rd paragraph states:
“We undertook a meta-analysis to test the hypothesis that rates of TB are different in BCG-vaccinated and BCG non-vaccinated control populations.”